Preparation and anti-tumor application of 9, 10-anthraquinone-(5-substituted salicylaldehyde) Schiff base dibutyltin complex

Abstract

The invention discloses a 9, 10-anthraquinone-(5-substituted salicylaldehyde) Schiff base dibutyltin complex which is a compound with the following structural formula (I): # imgabs0, and tin atoms in the molecule of the compound are of a pentacoordinate triangular bipyramid structure. The inventor also establishes a corresponding preparation method which comprises the following steps: by taking 2-amino-3-hydroxyanthraquinone, 5-substituted salicylaldehyde and dibutyltin oxide as raw materials and absolute methanol as a solvent, reacting under the condition of heating reflux. Researches show that the 9, 10-anthraquinone-(5-substituted salicylaldehyde) Schiff base dibutyltin complex has good inhibitory activity on human lung cancer cells, human liver cancer cells, human breast cancer cells and human oral cancer, and the in-vitro anticancer activity of the 9, 10-anthraquinone-(5-substituted salicylaldehyde) Schiff base dibutyltin complex is remarkably superior to that of a classic metal anticancer drug cis-platinum. Therefore, the compound has potential application value in research and development of anti-cancer drugs for human lung cancer, human liver cancer, human breast cancer and human oral cancer. In conclusion, the anthraquinone dibutyltin complex is good in anticancer activity, low in cost and simple in preparation method, and a new way is provided for developing new anticancer drugs.

Description

Technical Field

[0001] The present invention belongs to the technical field of anthraquinone derivatives, and particularly relates to the preparation and anti-tumor application of a 9,10-anthraquinone-(5-substituted salicylaldehyde) Schiff base dibutyltin complex. Background Art

[0002] Anthraquinone anti-tumor drugs are a class of classic chemotherapy drugs commonly used in clinics. Currently, the marketed anthraquinone anti-tumor drugs mainly include: Mitoxantrone, Doxorubicin, Daunorubicin, Idarubicin, Pixantrone, Valrubicin, etc., all of which have the same 9,10-anthraquinone parent nucleus structure. The 9,10-anthraquinone skeleton structure is the core for forming various anthraquinone anti-cancer drugs. In particular, its three-ring coplanar structure enables it to embed into the DNA double helix structure, thus serving as a DNA intercalator. Therefore, 9,10-anthraquinone is commonly used as the core skeleton for structural modification to develop new anthraquinone compounds as promising cancer therapeutic drugs.

[0003] Since the discovery of the first anthraquinone anti-cancer drug Doxorubicin in the 1940s of the 19th century, researchers have designed and synthesized a large number of new compounds based on the 9,10-anthraquinone skeleton structure. So far, the number of artificially synthesized 9,10-anthraquinone small molecule organic compounds has exceeded more than 10,000, accounting for more than 99% of all compounds containing the 9,10-anthraquinone skeleton structure. In recent years, medicinal chemists have developed some novel structures with high-efficiency and broad-spectrum anti-cancer activities based on the 9,10-anthraquinone skeleton structure. These anthraquinone derivatives have good inhibitory effects on the proliferation of various tumor cells, and some derivatives exhibit selective cytotoxicity and the ability to induce apoptosis.

[0004] In recent years, organotin complexes have attracted extensive attention due to their high-efficiency and broad-spectrum anticancer activities and low cytotoxicity. Currently, the anticancer activities of many organotin compounds have exceeded those of cisplatin or carboplatin widely used clinically, and some research results have obtained the protection of Chinese patents, US patents, and world patents. Therefore, organotin complexes are classified as anticancer drugs with great development potential. Among them, organotin(IV) complexes play a crucial role in the development of anticancer drugs. There are mainly two reasons: 1) Organotin(IV) complexes exhibit extremely high levels of anti-proliferative activity and are effective against various types of cancer cell lines. 2) The physicochemical properties of organotin(IV) complexes and their ability to form stable complexes. The anticancer activity of organotin(IV) complexes is not only related to the type and number of hydrocarbon groups connected to the tin atom but also closely related to the ligands. In addition, the high selectivity of organotin(IV) complexes for killing tumor cells and their low cytotoxicity to liver and kidney cells have become another research hotspot after platinum-based antitumor drugs and are a class of highly efficient and broad-spectrum anticancer new drugs with great development potential.

[0005] After investigation, the reports on the application of anticancer drugs involving anthraquinone derivatives or organotin compounds are as follows:

[0006] The Chinese patent application "An Anthraquinone Mother Nucleus Structure Compound, Its Preparation Method and Application" (Patent Application No. 2024107003413, Publication Date: September 13, 2024) discloses an anthraquinone mother nucleus structure compound, its preparation method and application. This compound is 1,8-dibenzyloxy-9,10-anthraquinone-N-(4-phenylethanol)-3-carboxamide, which can effectively inhibit the expression of MCL-1, significantly kill hepatocellular carcinoma cells with high expression of MCL-1 both in vivo and in vitro, and no obvious toxic effect on the heart is observed, providing a new and safe drug application route for the treatment of liver cancer.

[0007] The Chinese patent "An Anthraquinone Compound, Its Preparation Method and Application" (Patent No. 2021108311403, Publication Date: February 3, 2023) discloses an anthraquinone compound and its preparation method, and this compound has good application prospects in the field of biological activities and can be used as a potential anticancer drug and a new type of topoisomerase inhibitor drug.

[0008] The Chinese patent "A Dibutyltin Complex of 2-Carbonyl-2-Phenylacetic Acid Salicylhydrazone, Its Preparation Method and Application" (Patent No. 2015107777398, Publication Date: November 11, 2015) discloses a preparation method of a dibutyltin complex of 2-carbonyl-2-phenylacetic acid salicylhydrazone and its application in the preparation of anticancer drugs.

[0009] The Chinese patent "A p-chlorobenzoylhydrazone organotin complex and its preparation method and application" (Patent No. 2008101603513, publication date August 12, 2009) discloses a p-chlorobenzoylhydrazone organotin complex that can be used to prepare drugs for treating gastric cancer, nasopharyngeal cancer, human liver cancer or leukemia, providing a new approach for the development of anti-cancer drugs.

[0010] The literature (Eur. J. Med. Chem. 2025, 281: 117013.) reports a class of novel heteroarene-fused anthraquinone compounds with high anti-cancer activity. The synthesized compounds interact with double-stranded DNA and inhibit topoisomerase.

[0011] The literature (J. Med. Chem. 2024, 67: 4624 - 4640.) reports that a class of new anthraquinone compounds have strong cytotoxicity against various tumor cells and can insert into AT-rich DNA base pairs, thereby achieving selective cleavage of T and A bases.

[0012] When researchers modify the 9,10-anthraquinone skeleton structure, they almost all focus on synthesizing small organic molecules. However, there are few reports on substances that are organic tin complexes synthesized based on the 9,10-anthraquinone skeleton structure and can significantly improve the anti-cancer activity of anthraquinone. Summary of the Invention

[0013] The technical problem to be solved by the present invention is to provide a preparation method and anti-tumor application of a dibutyltin complex of 9,10-anthraquinone-(substituted salicylaldehyde) Schiff base.

[0014] To solve the above technical problems, the present invention adopts the following technical solutions:

[0015] The dibutyltin complex of 9,10-anthraquinone-(substituted salicylaldehyde) Schiff base is a compound of the following structural formula (I):

[0016]

[0017] Among them, R is -OH, -CH3, -C(CH3)3, -OCH3, -F, -Cl, -Br, -NO2.

[0018] When R is -OH, the complex is A1, and its crystal is triclinic, space group P-1, α = 76.9630(10)°, β = 80.0400(10)°,

[0019] γ = 88.1340(10)°, Z = 2, Dc = 1.599 Mg·m -3 ,

[0020] F(000) = 600.0; The tin atom in the molecule has a trigonal bipyramidal configuration with five coordination sites;

[0021] When R is -C(CH3)3, the complex is A3, and its crystal belongs to the triclinic system, space group P-1, α = 76.516(2)°, β = 82.108(2)°, γ = 80.637(2)°, Z = 4, Dc = 1.446 Mg·m -3 , F(000) = 1296.0; The tin atom in the molecule has a trigonal bipyramidal configuration with five coordination sites;

[0022] When R is -OCH3, the complex is A4, and its crystal belongs to the monoclinic system, space group P21 / c, α = 90°, β = 112.765(3)°, γ = 90°, Z = 4, Dc = 1.499 Mg·m -3 , F(000) = 1232.0; The tin atom in the molecule has a trigonal bipyramidal configuration with five coordination sites;

[0023] When R is -NO2, the complex is A8, and its crystal belongs to the tetragonal system, space group R3c, α = 90°, β = 90°, γ = 120°, Z = 18, Dc = 1.592 Mg·m -3 , F(000) = 5652.0; The tin atom in the molecule has a trigonal bipyramidal configuration with five coordination sites.

[0024] Use of the above-mentioned anthraquinone dibutyltin complex in the preparation of anti-tumor drugs.

[0025] The tumor is lung cancer, liver cancer, breast cancer or oral cancer.

[0026] Lung cancer, liver cancer, breast cancer and oral cancer originate from human lung cancer cell line A549, human liver cancer cell line HepG2, human breast cancer cell line MDA-MB-231 and human oral cancer cell line CAL-27 respectively.

[0027] Preparation method of the above-mentioned anthraquinone dibutyltin complex, using 2-amino-3-hydroxyanthraquinone, 5-substituted salicylaldehyde and dibutyltin oxide as raw materials, and using anhydrous methanol as a solvent, and reacting under the condition of heating and refluxing to complete.

[0028] The 5-substituted salicylaldehyde is 5-hydroxy salicylaldehyde, 5-methyl salicylaldehyde, 5-tert-butyl salicylaldehyde, 5-methoxy salicylaldehyde, 5-fluoro salicylaldehyde, 5-chloro salicylaldehyde, 5-bromo salicylaldehyde or 5-nitro salicylaldehyde.

[0029] The molar ratio of 2-amino-3-hydroxy anthraquinone, 5-substituted salicylaldehyde and dibutyltin oxide is 1:1:1.

[0030] In the above preparation method, 1 mmol of 2-amino-3-hydroxy anthraquinone, 1 mmol of 5-substituted salicylaldehyde, 1 mmol of dibutyltin oxide and 30 ml of anhydrous methanol as the solvent are added to a flask, and the reaction is carried out for 8 h under heating and reflux conditions, then cooled, filtered, and the solvent is volatilized and crystallized at room temperature to obtain the product.

[0031] Through in-depth research on the 9,10-anthraquinone skeleton structure compounds, the inventors designed and prepared a 9,10-anthraquinone-(5-substituted salicylaldehyde) Schiff base dibutyltin complex, which is a compound of the following structural formula (I):

[0032]

[0033] Wherein, R is -OH, -CH3, -C(CH3)3, -OCH3, -F, -Cl, -Br, -NO2. The tin atom in the compound molecule has a pentacoordinate trigonal bipyramidal configuration.

[0034] Accordingly, the inventors also established a corresponding preparation method, using 2-amino-3-hydroxy anthraquinone, 5-substituted salicylaldehyde and dibutyltin oxide as raw materials, and anhydrous methanol as the solvent, and the reaction is completed under heating and reflux conditions. In vitro anti-cancer activity studies have shown that the 9,10-anthraquinone-(5-substituted salicylaldehyde) Schiff base dibutyltin complex of the present invention has good inhibitory activity against human lung cancer cells, human liver cancer cells, human breast cancer cells and human oral cancer, and its in vitro anti-cancer activity is significantly better than that of the classical metal anti-cancer drug cisplatin. Therefore, it has potential application value in the research and development of anti-cancer drugs for human lung cancer, human liver cancer, human breast cancer and human oral cancer. In summary, the anthraquinone dibutyltin complex of the present invention has good anti-cancer activity, low cost and simple preparation method, providing a new way for the development of new anti-cancer drugs. Description of the Drawings

[0035] Figure 1 It is the HRMS spectrum of the organotin complex A1 prepared in Example 1.

[0036] Figure 2 It is the HRMS spectrum of the organotin complex A2 prepared in Example 2.

[0037] Figure 3HRMS spectrum of the organotin complex A3 prepared in Example 3.

[0038] Figure 4 HRMS spectrum of the organotin complex A4 prepared in Example 4.

[0039] Figure 5 HRMS spectrum of the organotin complex A5 prepared in Example 5.

[0040] Figure 6 HRMS spectrum of the organotin complex A6 prepared in Example 6.

[0041] Figure 7 HRMS spectrum of the organotin complex A7 prepared in Example 7.

[0042] Figure 8 HRMS spectrum of the organotin complex A8 prepared in Example 8.

[0043] Figure 9 Crystal structure diagram of the organotin complex A1 prepared in Example 1.

[0044] Figure 10 Crystal structure diagram of the organotin complex A3 prepared in Example 3.

[0045] Figure 11 Crystal structure diagram of the organotin complex A4 prepared in Example 4.

[0046] Figure 12 Crystal structure diagram of the organotin complex A8 prepared in Example 8. Detailed implementation manners

[0047] The following examples are further detailed descriptions of the present invention

[0048] Example 1 Preparation of dibutyltin complex A1 of 9,10-anthraquinone-(5-hydroxy salicylaldehyde) Schiff base

[0049] Add 1 mmol of 2-amino-3-hydroxy-9,10-anthraquinone, 1 mmol of 5-hydroxy salicylaldehyde, 1 mmol of dibutyltin oxide and 30 mL of anhydrous methanol as the solvent into a 50 mL round-bottom flask, heat under reflux for 8 h, cool, filter, and control the solvent evaporation and crystallization at room temperature to obtain a brownish-red transparent crystal, which is the dibutyltin complex A1 of 9,10-anthraquinone-(5-hydroxy salicylaldehyde) Schiff base. Yield: 83%.

[0050] Through nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, and X-ray single crystal diffraction structure analysis, the results are as follows:

[0051] 11H NMR (500 MHz, CDCl3) δ 8.80 - 8.66 (m, 1H), 8.27 (s, 1H), 8.23 - 8.06 (m, 2H), 7.71 (dd, J = 5.5, 3.3 Hz, 2H), 7.66 (s, 1H), 7.48 (s, 1H), 7.27 - 7.12 (m, 1H), 6.69 (dd, J = 21.2, 5.7 Hz, 2H), 1.79 - 1.49 (m, 8H), 1.43 - 1.23 (m, 4H), 0.85 (t, J = 7.3 Hz, 6H).

[0052] 13 13C NMR (126 MHz, CDCl3) δ 182.73, 182.58, 165.43, 164.78, 147.45, 136.95, 134.99, 133.91, 133.72, 128.52, 127.09, 123.65, 122.42, 118.29, 117.19, 116.34, 115.02, 26.94, 26.63, 22.61, 13.57.

[0053] 119 119Sn NMR (187 MHz, CDCl3) δ -176.21.

[0054] HRMS (ESI) m / z calcd for C 29 H 29 NO5NaSn + [M + Na] + 614.0965, found 614.0969.

[0055] Crystallographic data: Triclinic system, space group P - 1, α = 76.9630(10)°, β = 80.0400(10)°, γ = 88.1340(10)°, Z = 2, Dc = 1.599 Mg·m -3 , F(000) = 600.0; The tin atom in the molecule has a pentacoordinate trigonal bipyramidal configuration.

[0056] Example 2 Preparation of dibutyltin complex A2 of 9,10 - anthraquinone - (5 - methylsalicylaldehyde) Schiff base

[0057] Add 1 mmol of 2-amino-3-hydroxy-9,10-anthraquinone, 1 mmol of 5-methylsalicylaldehyde, 1 mmol of dibutyltin oxide and 30 mL of anhydrous methanol as the solvent into a 50 mL round-bottom flask. Heat under reflux for 8 h, cool, filter, and control the solvent to volatilize and crystallize at room temperature to obtain a brownish-red transparent crystal, which is the dibutyltin complex A2 of 9,10-anthraquinone-(5-methylsalicylaldehyde) Schiff base. Yield: 89%.

[0058] The results of nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry structure analysis are as follows:

[0059] 1 H NMR(500MHz,CDCl3)δ8.92-8.79(m,1H),8.37-8.20(m,3H),7.79-7.71(m,2H),7.59(s,1H),7.31-7.26(m,1H),7.11(s,1H),6.73(d,J=8.6Hz,1H),2.29(s,3H),1.76-1.46(m,8H),1.40-1.22(m,4H),0.85(t,J=7.3Hz,6H).

[0060] 13 C NMR(126MHz,CDCl3)δ183.15,181.89,169.12,165.00,164.81,140.28,137.01,134.93,134.09,133.94,133.79,133.44,127.05,127.00,126.70,123.01,122.66,117.25,116.06,114.56,26.93,26.58,22.44,20.14,13.55.

[0061] 119 Sn NMR(187MHz,CDCl3)δ-177.40.

[0062] HRMS(ESI)m / z calcd for C 30 H 32 NO4Sn + [M+H] + 590.1353,found 590.1356.

[0063] Example 3 Preparation of dibutyltin complex A3 of 9,10-anthraquinone-(5-tert-butylsalicylaldehyde) Schiff base

[0064] 1 mmol of 2-amino-3-hydroxy-9,10-anthraquinone, 1 mmol of 5-tert-butylsalicylaldehyde, 1 mmol of dibutyltin oxide and 30 mL of anhydrous methanol as the solvent were added to a 50 mL round-bottom flask. The mixture was heated under reflux for 8 h, cooled, filtered, and the solvent was allowed to evaporate at room temperature to crystallize, yielding a brownish-red transparent crystal, which is the dibutyltin complex A4 of 9,10-anthraquinone-(5-tert-butylsalicylaldehyde) Schiff base. Yield: 87%.

[0065] The results of nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, and X-ray single crystal diffraction structure analysis are as follows:

[0066] 1 H NMR (500 MHz, CDCl3) δ 8.99 - 8.87 (m, 1H), 8.41 - 8.21 (m, 3H), 7.83 - 7.72 (m, 2H), 7.68 - 7.51 (m, 2H), 7.28 (t, J = 5.1 Hz, 1H), 6.78 (d, J = 8.9 Hz, 1H), 1.76 - 1.47 (m, 8H), 1.41 - 1.29 (m, 13H), 0.85 (t, J = 7.3 Hz, 6H).

[0067] 13 C NMR (126 MHz, CDCl3) δ 183.15, 181.94, 169.15, 165.20, 164.97, 140.21, 137.13, 137.02, 134.88, 134.10, 133.96, 133.78, 133.44, 131.42, 127.05, 127.01, 122.98, 122.51, 116.72, 116.06, 114.44, 33.94, 31.11, 26.91, 26.59, 22.56, 13.55.

[0068] 119 Sn NMR (187 MHz, CDCl3) δ -177.01.

[0069] HRMS (ESI) m / z calcd for C 33 H 38 NO4Sn + [M + H] + 632.1823, found 632.1827.

[0070] Crystallographic data: Triclinic system, space group P-1, α = 76.516(2)°, β = 82.108(2)°, γ = 80.637(2)°, Z = 4, Dc = 1.446 Mg·m -3 , F(000) = 1296.0; The tin atom in the molecule has a trigonal bipyramidal configuration with five coordination sites.

[0071] Example 4 Preparation of 9,10-anthraquinone-(5-methoxysalicylaldehyde) Schiff base dibutyltin complex A4

[0072] Add 1 mmol of 2-amino-3-hydroxy-9,10-anthraquinone, 1 mmol of 5-methoxysalicylaldehyde, 1 mmol of dibutyltin oxide and 30 mL of anhydrous methanol as the solvent into a 50 mL round-bottom flask. Heat under reflux for 8 h, cool, filter, and control the solvent evaporation and crystallization at room temperature to obtain a brown-red transparent crystal, which is 9,10-anthraquinone-(5-methoxysalicylaldehyde) Schiff base dibutyltin complex A5. Yield: 88%.

[0073] Through nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, and X-ray single crystal diffraction structure analysis, the results are as follows:

[0074] 1 1H NMR (500 MHz, CDCl3) δ 8.92 - 8.80 (m, 1H), 8.26 (dd, J = 14.1, 8.3 Hz, 3H), 7.83 - 7.69 (m, 2H), 7.59 (s, 1H), 7.15 (dd, J =9.2, 2.9 Hz, 1H), 6.74 (dd, J = 19.6, 6.0 Hz, 2H), 3.83 (s, 3H), 1.76 - 1.45 (m, 8H), 1.40 - 1.23 (m, 4H), 0.86 (t, J = 7.3 Hz, 6H).

[0075] 13 13C NMR (126 MHz, CDCl3) δ 183.11, 181.89, 166.69, 164.94, 164.16, 150.92, 137.02, 134.92, 134.06, 133.94, 133.78, 133.45, 129.49, 127.05, 126.99, 124.08, 123.02, 116.41, 116.05, 114.53, 114.01, 55.85, 26.93, 26.58, 22.44, 13.56.

[0076] 119 119Sn NMR (187 MHz, CDCl3) δ -176.10.

[0077] HRMS (ESI) m / z calcd for C 30 H 32NO5Sn + [M+H] + 606.1302, found 606.1309.

[0078] Crystallographic data: Monoclinic system, space group P21 / c, α = 90°, β = 112.765(3)°, γ = 90°, Z = 4, Dc = 1.499 Mg·m -3 , F(000) = 1232.0; The tin atom in the molecule has a pentacoordinate trigonal bipyramidal configuration.

[0079] Example 5 Preparation of 9,10-anthraquinone-(5-fluorosalicylaldehyde) Schiff base dibutyltin complex A5

[0080] Add 1 mmol of 2-amino-3-hydroxy-9,10-anthraquinone, 1 mmol of 5-fluorosalicylaldehyde, 1 mmol of dibutyltin oxide and 30 mL of anhydrous methanol as the solvent to a 50 mL round-bottom flask, heat under reflux for 8 h, cool, filter, and control the solvent evaporation and crystallization at room temperature to obtain a brownish-red transparent crystal, which is 9,10-anthraquinone-(5-fluorosalicylaldehyde) Schiff base dibutyltin complex A5. Yield: 81%.

[0081] The results of nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry structure analysis are as follows:

[0082] 1 H NMR(500 MHz, CDCl3) δ 8.97–8.75(m, 1H), 8.26(dd, J = 12.6, 9.0 Hz, 3H), 7.81–7.70(m, 2H), 7.59(s, 1H), 7.23(td, J = 9.2, 3.1 Hz, 1H), 7.04(dd, J = 8.3, 3.0 Hz, 1H), 6.78(dd, J = 9.3, 4.4 Hz, 1H), 1.77–1.47(m, 8H), 1.42–1.24(m, 4H), 0.86(t, J = 7.3 Hz, 6H).

[0083] 13 C NMR(126 MHz, CDCl3) δ 183.05, 181.77, 167.40, 164.99, 163.93(d, J F-C = 2.8 Hz), 154.07(d, J F-C = 237.0 Hz), 136.52, 135.27, 134.02, 133.88, 133.52, 127.08, 127.04, 126.85(d, JF-C = 24.3 Hz), 124.19 (d, J F-C = 7.2 Hz), 123.09, 118.38 (d, J F-C = 22.4 Hz), 116.50 (d, J F-C = 8.1 Hz), 116.30, 114.87, 26.91, 26.58, 22.60, 13.54.

[0084] 119 Sn NMR (187 MHz, CDCl3) δ -177.07. 19 F NMR (471 MHz, CDCl3) δ -126.79.

[0085] HRMS (ESI) m / z calcd for C 29 H 29 FNO4Sn + [M + H] + 594.1103, found 594.1107.

[0086] Example 6 Preparation of 9,10-anthraquinone-(5-chlorosalicylaldehyde) Schiff base dibutyltin complex A6

[0087] Add 1 mmol of 2-amino-3-hydroxy-9,10-anthraquinone, 1 mmol of 5-chlorosalicylaldehyde, 1 mmol of dibutyltin oxide and 30 mL of anhydrous methanol as the solvent to a 50 mL round-bottom flask, heat under reflux for 8 h, cool, filter, and control the solvent evaporation to crystallize at room temperature to obtain a brownish-red transparent crystal, which is 9,10-anthraquinone-(5-chlorosalicylaldehyde) Schiff base dibutyltin complex A6. Yield: 83%.

[0088] The results of nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry structure analysis are as follows:

[0089] 1 H NMR (500 MHz, CDCl3) δ 8.95 - 8.74 (m, 1H), 8.45 - 8.09 (m, 3H), 7.91 - 7.70 (m, 2H), 7.59 (s, 1H), 7.46 - 7.29 (m, 2H), 6.77 (d, J = 9.0 Hz, 1H), 1.84 - 1.47 (m, 8H), 1.41 - 1.17 (m, 4H), 0.86 (t, J = 7.3 Hz, 6H).

[0090] 1313C NMR(126MHz,CDCl3)δ183.03,181.75,169.23,164.99,163.87,138.20,136.46,135.32,134.02,133.90,133.82,133.53,127.10,127.06,124.47,123.15,121.81,118.08,116.38,114.86,26.89,26.57,22.72,13.54.

[0091] 119 119Sn NMR(187MHz,CDCl3)δ -176.96.

[0092] HRMS(ESI)m / z calcd for C 29 H 29 ClNO4Sn + [M + H] + 610.0807, found 610.0801.

[0093] Example 7 Preparation of 9,10 - anthraquinone-(5 - bromosalicylaldehyde) Schiff base dibutyltin complex A7

[0094] Add 1 mmol of 2 - amino - 3 - hydroxy - 9,10 - anthraquinone, 1 mmol of 5 - bromosalicylaldehyde, 1 mmol of dibutyltin oxide and 30 mL of anhydrous methanol as solvent into a 50 mL round - bottom flask. Heat under reflux for 8 h, cool, filter, and control the solvent evaporation for crystallization at room temperature to obtain a brown - red transparent crystal, which is 9,10 - anthraquinone-(5 - bromosalicylaldehyde) Schiff base dibutyltin complex A7. Yield: 85%.

[0095] The results of nuclear magnetic resonance spectroscopy and high - resolution mass spectrometry structure analysis are as follows:

[0096] 1 1H NMR(500MHz,CDCl3)δ8.92 - 8.73(m,1H),8.25(dd,J = 13.1,10.0Hz,3H),7.79 - 7.68(m,2H),7.57(s,1H),7.47(dd,J = 4.5,2.2Hz,2H),6.78 - 6.60(m,1H),1.76 - 1.48(m,8H),1.40 - 1.26(m,4H),0.86(t,J = 7.3Hz,6H).

[0097] 1313C NMR(126 MHz, CDCl3) δ 182.98, 181.67, 169.53, 164.97, 163.84, 140.72, 137.07, 136.43, 135.29, 133.99, 133.89, 133.86, 133.51, 127.07, 127.05, 124.79, 123.13, 118.93, 116.36, 114.86, 108.41, 26.89, 26.58, 22.74, 13.56.

[0098] 119 119Sn NMR(187 MHz, CDCl3) δ -177.18.

[0099] HRMS(ESI) m / z calcd for C 29 H 29 BrNO4Sn + [M + H] + 654.0302, found 654.0297. Preparation of dibutyltin complex A8 of 9,10-anthraquinone-(5-nitrosalicylaldehyde) Schiff base

[0100] Add 1 mmol of 2-amino-3-hydroxy-9,10-anthraquinone, 1 mmol of 5-nitrosalicylaldehyde, 1 mmol of dibutyltin oxide and 30 mL of anhydrous methanol as the solvent into a 50 mL round-bottom flask, heat under reflux for 8 h, cool, filter, and control the solvent evaporation and crystallization at room temperature to obtain a brownish-red transparent crystal, which is the dibutyltin complex A8 of 9,10-anthraquinone-(5-nitrosalicylaldehyde) Schiff base. Yield: 92%.

[0101] The results of nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, and X-ray single crystal diffraction structure analysis are as follows:

[0102] 1 1H NMR(500 MHz, CDCl3) δ 9.20 - 8.95(m, 1H), 8.45(d, J = 2.6 Hz, 1H), 8.41 - 8.15(m, 4H), 7.89 - 7.70(m, 2H), 7.62(s, 1H), 6.84(d, J = 9.4 Hz, 1H), 1.77

[0103] - 1.53(m, 8H), 1.43 - 1.23(m, 4H), 0.87(t, J = 7.3 Hz, 6H).

[0104] 1313C NMR (126 MHz, CDCl3) δ 182.89, 181.58, 174.51, 164.88, 164.19, 138.30, 135.80, 134.06, 133.95, 133.83, 133.69, 133.17, 131.91, 127.16, 123.56, 123.41, 116.80, 116.19, 115.19, 26.81, 26.56, 23.31, 13.52.

[0105] 119 119Sn NMR (187 MHz, CDCl3) δ -174.51.

[0106] HRMS (ESI) m / z calcd for C 29 H 28 N2O6NaSn + [M + Na] + 643.0867, found 643.0868.

[0107] Crystallographic data: tetragonal system, space group R3c, α = 90°, β = 90°, γ = 120°, Z = 18, Dc = 1.592 Mg·m -3 , F(000) = 5652.0; The tin atom in the molecule has a trigonal bipyramidal configuration with five - coordinate.

[0108] Application example: Test for the proliferation - promoting effect of the compound on tumor cells by MTT method

[0109] Human lung cancer (A549), human liver cancer (HepG2), human breast cancer (MDA - MB - 231) and human oral cancer (CAL - 27) cells in the logarithmic growth phase were inoculated into 96 - well culture plates at a density of 3 - 5×10 3 cells / well. After the cells adhered for 24 h, the original culture medium was carefully discarded. In the negative control group, 100 μL of culture medium was added. In the experimental groups, 100 μL of compound solutions with different concentrations were added respectively. In the positive control groups, 100 μL of drug solutions with different concentrations were added respectively. Three parallel replicates were set for each concentration. The plates were incubated in an incubator at 37 °C and 5% CO2 for another 48 h. Then, 20 μL of MTT solution with a concentration of 5 mg·L -1 was added to each well and incubated for another 4 h. The supernatant was carefully discarded, 100 μL of DMSO was added to each well to dissolve, and shaken at low speed for 10 min. The absorbance value (OD value) of each well was measured at a wavelength of 490 nm using a full - automatic microplate reader. The inhibition rate of cell growth was calculated according to the following formula.

[0110] Cell growth inhibition rate % = [1 - (OD value of the drug - added group / OD value of the blank group)] × 100%.

[0111] The results are shown in Table 1, and the conclusion is: As can be seen from the data in the table, when the 9,10 - anthraquinone - (5 - substituted salicylaldehyde) Schiff base dibutyltin complex of the present invention is used as an anticancer drug, it has certain pharmacological effects on human lung cancer (A549), human liver cancer (HepG2), human breast cancer (MDA - MB - 231) and human oral cancer (CAL - 27) cells. The anticancer activities of all complexes are superior to those of the positive control drug cisplatin. Therefore, it can be used as a candidate compound for anticancer drugs and has potential application value.

[0112] Table 1 Effects of different complexes on the in vitro proliferation of different cancer cells

[0113]

Claims

1. A 9,10-anthraquinone-(5-substituted salicylaldehyde) Schiff base dibutyltin complex, characterized in that A compound of the following structural formula (I): Wherein, R is -OH, -CH3, -C(CH3)3, -OCH3, -F, -Cl, -Br, -NO2.

2. The anthraquinone dibutyltin complex according to claim 1, characterized in that:[[]]END]] When R is -OH, the complex is A1, and its crystal belongs to the triclinic system, space group P-1, α = 76.9630(10)°, β = 80.0400(10)°, γ = 88.1340(10)°, Z = 2, Dc = 1.599 Mg·m -3 , F(000) = 600.0; the tin atom in the molecule has a pentacoordinate trigonal bipyramidal configuration; When R is -C(CH3)3, the complex is A3, and its crystal is triclinic system with the space group P-1, α = 76.516(2)°, β = 82.108(2)°, γ = 80.637(2)°, Z = 4, Dc = 1.446 Mg·m -3 , F(000) = 1296.0; the tin atom in the molecule has a five-coordinate trigonal bipyramidal configuration; When R is -OCH3, the complex is A4, and its crystal is monoclinic system, space group P21 / c, α = 90°, β = 112.765(3)°, γ = 90°, Z = 4, Dc = 1.499 Mg·m -3 , F(000) = 1232.0; the tin atom in the molecule has a five - coordinate trigonal bipyramidal configuration; When R is -NO2, the complex is A8, and its crystal is tetragonal system with the space group R3c, α = 90°, β = 90°, γ = 120°, Z = 18, Dc = 1.592 Mg·m -3 , F(000) = 5652.0; the tin atom in the molecule has a five - coordinate trigonal bipyramidal configuration.

3. Use of the anthraquinone dibutyltin complex according to claim 1 in the preparation of anti-tumor drugs.

4. The application according to claim 3, characterized in that: The tumor is lung cancer, liver cancer, breast cancer or oral cancer.

5. The application according to claim 4, characterized in that: The lung cancer, liver cancer, breast cancer, and oral cancer are respectively derived from human lung cancer cell line A549, human liver cancer cell line HepG2, human breast cancer cell line MDA-MB-231, and human oral cancer cell line CAL-27.

6. The preparation method of the anthraquinone dibutyltin complex according to claim 1, characterized in that: Using 2-amino-3-hydroxyanthraquinone, 5-substituted salicylaldehyde and dibutyltin oxide as raw materials, and anhydrous methanol as the solvent, the reaction is completed under the condition of heating under reflux.

7. The preparation method according to claim 6, wherein: The 5-substituted salicylaldehyde is 5-hydroxy salicylaldehyde, 5-methyl salicylaldehyde, 5-tert-butyl salicylaldehyde, 5-methoxy salicylaldehyde, 5-fluoro salicylaldehyde, 5-chloro salicylaldehyde, 5-bromo salicylaldehyde or 5-nitro salicylaldehyde.

8. The preparation method according to claim 6, characterized in that: The molar ratio of 2-amino-3-hydroxyanthraquinone, 5-substituted salicylaldehyde and dibutyltin oxide is 1:1:

1.

9. The preparation method according to claim 8, wherein: Add 1 mmol of 2-amino-3-hydroxyanthraquinone, 1 mmol of 5-substituted salicylaldehyde, 1 mmol of dibutyltin oxide and 30 ml of anhydrous methanol as the solvent into a flask, react for 8 h under the condition of heating under reflux, cool, filter, and control the solvent to volatilize and crystallize at room temperature to obtain the product.

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